The effect of histamine on adrenergic neurotransmission in the mouse isolated vas deferens preparation was investigated. Concentrations of histamine ranging from 0.2 to 650 microM depressed, in a dose-related manner, not only the contractile response elicited by field stimulation but also the response caused by the addition of exogenous noradrenaline and acetylcholine. However, the release of [3H]-NA evoked by field stimulation or by high K+ remained unchanged in the presence of these concentrations of histamine. The inhibitory effect of histamine on the contractile responses caused by various stimuli was reduced or completely antagonized by cimetidine, a histamine H2-receptor antagonist but not by mepyramine, a conventional antihistamine. The inhibitory effect of histamine was found to be inversely proportional to both the Ca2+ concentration in the bathing medium and to the frequency of field stimulation. Further, the inhibitory effect of histamine was markedly reduced when Mg2+ was omitted from the bathing medium. It is concluded that the mouse vas deferens preparation contains a post-junctional inhibitory H2-receptor. The stimulation of H2-receptors by histamine inhibits the contractile response of the vas deferens, possibly by decreasing the availability of Ca2+ required for contraction by depressing the influx of Ca2+.

Histamine, specific H1- and H2-receptor agonists in conjunction with specific H1- and H2-receptor antagonists and other types of classical antagonists were used to characterize histamine receptors in the vasa deferentia of mice, rats and guinea pigs. The H1-receptor mediates contraction while the H2-receptor produces inhibition. There were marked qualitative and quantitative differences in the distribution of the two types of histamine receptors in the vas deferens of different species. Results indicate that mouse and rat vas deferens contain an inhibitory H2-receptor, but virtually no excitatory H1-receptor. In contrast, guinea pig vas deferens contained an excitatory H1-receptor but was essentially devoid of an inhibitory H2-receptor. The rank order of relative potencies of various agonists as well as the calculated pA2 values of cimetidine in the mouse and rat vas deferens suggest that the two species probably have athe same H2-receptor. High concentrations of histamine and 2-methyl histamine have a stimulant action in the mouse and rat vas deferens which was secondary to release of endogenous noradrenaline rather than to the stimulation of an excitatory H1-receptor.

of peptic ulcer disease. Can J Gastroenterol 1991 ;5( 1):21-33. The etiology of peptic ulcer is multifactorial; except for omeprazole, all drugs used for the treatment of peptic ulcer result in healing with no statistical difference at four weeks. The healing rare increases with time for active medication and placebo, and is lower among smokers than nonsmokers for all drugs but misoprostol. Mucosa[ protectives (or 'cytoprotectives') as a group seem to have a lowe r relapse rate than the Hz receptor antagonists at one year. Combination therapy h as not yet proved to be better than single drug therapy; however, the number of studies is still small, and more clinical trials are necessary. Resistant ulcers have demonstrated that acid is one of several etiological factors and that more research is needed to elucidate the reason(s) for refractoriness. The choice of therapeutic agent is generally made according to patient compliance, medication cost, side effects, effectiveness, relapse rate and physician experience with the drug. Long term maintenance therapy is effective in the prevention of ulcer relapse and is especially recommended for selected patient groups, including patients with recurrent or bleeding ulcer, patients with concomitant nonste ro idal anti-inflammatory drug use, and elderly women. Omeprazole is the treatment of choice for moderate to severe esophagitis and should be reserved for large and resistant ulcers.

This review analyzes the results of recent studies of the actions of cholinomimetic drugs on adrenergic nerve terminals and their implications for the cholinergic link hypothesis. Thus far, evidence suggests that the only possible action of endogenous acetylcholine (ACh) present near noradrenaline (NA) stores is an inhibition of the release of NA from the adrenergic nerve terminals and that NA is released only when the action of acetylcholinesterase is inhibited. Nicotinic agents have been shown to act on adrenergic nerve terminal membranes, a finding that casts doubt on the proposed intraneuronal cholinergic sites for the action of endogenous ACh. Evidence also indicates that the mode of adrenergic neurone blocking action of bretylium and guanethidine is independent of the proposed cholinergic process in NA release. Current findings do not support the proposal that nicotinic agents in higher concentrations interfere with adrenergic neurotransmission. It is therefore concluded that nicotinic agents, in causing the release of NA from adrenergic nerve terminals, are merely exhibiting a pharmacological action and not mimicking the physiological function of ACh, as proposed by the cholinergic link hypothesis.